PLoS pathogens, 2017-07, Vol.13 (7), p.e1006506
2017
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- Autor(en) / Beteiligte
- Titel
- KIR3DL01 upregulation on gut natural killer cells in response to SIV infection of KIR- and MHC class I-defined rhesus macaques
- Ist Teil von
- PLoS pathogens, 2017-07, Vol.13 (7), p.e1006506
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues. NK cell responses in blood were broadly stimulated, as indicated by rapid increases in the CD16+ population during acute infection and sustained increases in the CD16+ and CD16-CD56- populations during chronic infection. Markers of proliferation (Ki-67), activation (CD69 & HLA-DR) and antiviral activity (CD107a & TNFα) were also widely expressed, but began to diverge during chronic infection, as reflected by sustained CD107a and TNFα upregulation by KIR3DL01+, but not by KIR3DL05+ NK cells. Significant increases in the frequency of KIR3DL01+ (but not KIR3DL05+) NK cells were also observed in tissues, particularly in the gut-associated lymphoid tissues, where this receptor was preferentially upregulated on CD56+ and CD16-CD56- subsets. These results reveal broad NK cell activation and dynamic changes in the phenotypic properties of NK cells in response to SIV infection, including the enrichment of KIR3DL01+ NK cells in tissues that support high levels of virus replication.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1006506Titel-ID: cdi_plos_journals_1929430557
- Format
- –
- Schlagworte
- Animals, Antiviral activity, Biology and life sciences, Blood, Cancer, CD16 antigen, CD56 antigen, CD69 antigen, Cell activation, Cell Degranulation, Cell Proliferation, Chronic infection, Cytokines - immunology, Cytotoxicity, Female, Gastrointestinal Tract - immunology, Gastrointestinal Tract - virology, Genetic aspects, Gut-associated lymphoid tissues, Health aspects, Histocompatibility antigen HLA, Histocompatibility Antigens Class I - genetics, Histocompatibility Antigens Class I - immunology, Immune response regulation, Immunoglobulin-like receptors, Immunoglobulins, Infections, Killer cell immunoglobulin-like receptors, Killer cells, Killer Cells, Natural - cytology, Killer Cells, Natural - immunology, Laboratory animals, Ligands, Lymphoid tissue, Lymphoid Tissue - immunology, Macaca mulatta, Major histocompatibility complex, Male, Medical research, Medicine, Medicine and health sciences, Monkeys & apes, Natural killer cells, Pathogens, Pathology, Peripheral blood, Potassium channels (inwardly-rectifying), Primates, Receptors, Receptors, KIR3DL1 - genetics, Receptors, KIR3DL1 - immunology, Research and Analysis Methods, Simian Acquired Immunodeficiency Syndrome - genetics, Simian Acquired Immunodeficiency Syndrome - immunology, Simian Acquired Immunodeficiency Syndrome - physiopathology, Simian Acquired Immunodeficiency Syndrome - virology, Simian immunodeficiency virus, Simian Immunodeficiency Virus - physiology, Target recognition, Tissues, Transcription factors, Tumor necrosis factor, Up-Regulation, Viruses